Arsenic in Food

Elizabeth Streit wrote . . . . . . . . .

Historically, arsenic has been viewed as a dangerous substance with fatal consequences. While arsenic has long been used as a poison, it’s also a naturally occurring metalloid. Thus, humans are regularly exposed to arsenic via food, water, air, and soil.

Long-term exposure to arsenic has been linked to an increased risk of certain cancers, heart disease, high blood pressure, issues with blood sugar regulation, and neurodevelopmental problems. However, the effects of arsenic consumption largely depend on the level of exposure.

These potential effects of arsenic make its presence in the food supply a concern for both food producers and consumers. The FDA and Environmental Protection Agency (EPA) have developed regulations and recommendations to help limit human exposure to arsenic.

This continuing education course reviews the estimated levels of arsenic in the food supply, the links between arsenic exposure and disease, populations at risk, and recommendations for limiting exposure. It also explains the difference between organic and inorganic arsenic compounds, the latter considered more toxic to humans. A review of the existing research on the health effects of arsenic, regulations on arsenic levels in food and water, and current recommendations for clinicians to use in practice are included.

Arsenic in the Food Supply

Arsenic exists in the food supply as inorganic and organic compounds. Inorganic forms of arsenic include arsenite and arsenate, which are considered more toxic to humans than organic compounds. In the body, these compounds undergo methylation by kidney and liver enzymes to become monomethylarsonic acid and dimethylarsinic acid, both of which may exhibit potentially hazardous effects on organ systems.

Organic arsenic compounds, such as arsenobetaine, usually aren’t considered toxic at levels typically consumed. These are found in freshwater and marine fish, which consume biota that take up inorganic arsenic and transform it to organic forms of arsenic that are then stored in the tissues of the fish. Most fish will have some level of inorganic arsenic in addition to organic forms, but seaweed, mussels, and some other shellfish tend to be much higher in inorganic arsenic than are larger fish. Supplement products derived from certain seaweeds also may contain higher amounts of inorganic arsenic.

Arsenic exists generally in small amounts in the environment, depending on the industries present in the area, as well as the geological makeup in a certain location. It can be found in soil, water, or air and eventually end up in the food supply.

Since arsenic occurs naturally in the earth’s crust, it can be released into the air, soil, or groundwater through volcanoes, fracking, and erosion. Arsenic also infiltrates the environment by way of pollution, especially from dusts produced by extracting copper from its ore and coal burning. The majority of arsenic in drinking water comes from the erosion of geological sources or combustion, metal extraction, and industrial run-off.

Much of the arsenic present in the food supply is the result of the use of arsenic-based pesticides and wood preservatives. Pesticides with inorganic arsenic haven’t been in use for more than 50 years in the United States, but their residues may exist in the soil of millions of acres of land. Because arsenic dissolves easily in water, these residues make their way into water used for drinking and farming by way of run-off. Thus, contamination in both soil and water is responsible for arsenic in foods. Some pesticides and fertilizers with organic forms of arsenic are used today.

Because arsenic is present in varying amounts in soils all over the world, almost all plant foods grown in soil will contain some arsenic. Studies show that the roots of lettuces, broad beans, and leafy green vegetables take up arsenic from soil. The safe threshold for the amount of arsenic in these foods appears to be largely dependent on the soil characteristics of the location. Arsenic also may be more concentrated in certain parts of vegetables, such as in the skin of root vegetables compared with the flesh.

Rice, leafy greens and other vegetables, fruit juices such as apple juice, fruits, beer, wine, flour, corn, and wheat are the largest contributors of inorganic arsenic in the US diet, but this doesn’t necessarily mean that each food group contains dangerously high amounts. In the past, arsenic levels in poultry in the United States have been a concern due to the use of arsenic-based drugs in raising chickens. However, since 2015, these drugs are no longer approved by the FDA for this use.

Apple and fruit juices often are singled out as a possible source of dangerous levels of arsenic in the diet. Fruit juices may have higher levels of arsenic than does whole fruit because they’re made from several pieces of fruit. However, analyses of apple juice samples by the FDA suggest that their levels of inorganic arsenic generally aren’t concerning. Still, exposure to arsenic from apple and other juices can be curbed by limiting consumption of fruit juice and eating a varied diet.

Rice may contain high amounts of inorganic arsenic because of its growing environment. Rice paddies are intentionally flooded with water, which in turn can bring arsenic into the plants. Rice also may be grown in areas with soil historically treated with large amounts of arsenic-based pesticides. Rice from the southern United States, grown on old cotton fields treated with these pesticides in the past, often contains more arsenic than does rice grown in California. Certain regions of the world, especially South Asia, also produce rice with greater arsenic levels due to high amounts of arsenic in the groundwater from the erosion of arsenic-containing rocks and materials in aquifers.

All types of rice contain some amount of arsenic, but brown rice has more than white varieties. Arsenic accumulates in rice bran, which isn’t removed from brown rice. Despite confusion resulting from use of the terms “inorganic” or “organic” arsenic, rice grown with organic methods doesn’t have less arsenic than does conventional rice. Products derived from rice, such as rice milk, rice bran, brown rice syrup, and rice cereal for babies, also are sources of inorganic arsenic in the food supply.

Current Regulations

The variability of arsenic levels in food and drinking water and the differences in consumption across the United States present challenges to creating regulations. While the detrimental effects of high doses of arsenic are well known, the effects of prolonged exposure to lower amounts in the food and water supply are less clear. As a result, few foods are subject to regulations on arsenic concentrations in the United States, and consumers may feel that they don’t have enough information to guide their decisions about arsenic in the food supply.

The existing regulations upheld by the EPA and FDA aim to reduce human exposure to inorganic arsenic. The EPA regulates arsenic levels in drinking water, while the FDA has set regulations for bottled water and recommendations for infant rice cereal and apple juice.

As of 2001, the EPA maximum contaminant level (MCL) for inorganic arsenic in US drinking water supplies is 10 parts per billion (ppb), which translates to approximately 0.010 mg (10 mcg) per liter. This replaces the old standard of 50 ppb, which a 1999 report from the National Academy of Sciences suggested didn’t protect public health. All community water systems must be monitored and tested regularly for arsenic levels. If they exceed 10 ppb, the EPA provides resources related to treatment and mitigation strategies. At the time of implementing the MCL, the EPA estimated that in order to decrease arsenic levels, changes would need to be made to approximately 5% of water systems serving roughly 11 million citizens.

While the majority of water systems in the United States haven’t reported inorganic arsenic levels at or above 10 ppb, some western states, parts of New England, and the Midwest may have levels that exceed the EPA standard. Arsenic levels tend to be higher in groundwater sources of drinking water compared with surface water sources, such as lakes and rivers. Wells, which draw from groundwater, also may present a problem. Some research suggests that hot spot areas served by privately owned domestic wells exist in more than 25 states, with 2.1 million people possibly exposed to high levels of arsenic.

In response to the EPA’s standard, the FDA established a similar allowable level for inorganic arsenic in bottled water in 2005. This level is also 10 ppb or 0.01 mg (10 mcg) per liter of water.

There are few regulations and no enforceable maximum levels of inorganic arsenic, even though food may contribute more than water to total inorganic arsenic exposure. Contaminated water used for crop irrigation may contribute to the build-up of arsenic in certain foods, but no federal agency regulates these levels. For arsenic in apple juice and infant rice cereal, the FDA has published draft guidance documents that reflect the FDA’s current assessment of a topic and provide recommendations but not legal requirements. The recommendation for inorganic arsenic in apple juice is 10 ppb, or 0.01 mg/L. For infant rice cereal, inorganic arsenic should be below 100 ppb. These amounts are considered action levels, meaning the FDA samples apple juice and infant rice cereals; if it finds high inorganic arsenic levels, it may consider enforcing the recommendations. In the FDA’s most recent report on 94 retail apple juice samples, all products had less than 10 ppb of inorganic arsenic. The agency’s data from infant rice cereal sampling in 2018 showed that 76% of samples were at or below 100 ppb of inorganic arsenic, compared with only 47% of samples in 2014.

Estimated Intakes

Evaluating an individual or population’s dietary arsenic level involves identifying what foods and drinks contain inorganic or organic arsenic and how much is consumed. The estimated daily intake of arsenic then can be compared with the EPA’s oral reference dose (RfD) of 0.3 mcg of inorganic arsenic per kilogram of body weight per day, or maximum intake of a toxic substance that likely won’t result in negative health effects.

Arsenic levels vary widely from food to food, making estimations of arsenic intake difficult. For example, products made from rice grown in areas with high levels of arsenic in the soil and water may have significantly more arsenic than do similar products grown in a different area. In the absence of an extensive database that provides information on arsenic levels in foods and distinguishes between organic and inorganic forms, identifying problematic foods isn’t always possible.

Based on the research that has been done, most food and drink products in the United States don’t contain concerning levels of inorganic arsenic in the amounts they’re consumed. In addition, the US population on average doesn’t consume levels above the EPA’s RfD.28 Still, problems may arise when individuals are exposed to multiple sources of high levels of inorganic arsenic, for example, in communities that have contaminated groundwater and eat large amounts of rice.

Mantha and colleagues examined the inorganic arsenic concentrations in drinking water utilities and rice, using a 2010 EPA review that included utilities from 47 states, as well as 54 samples of rice from US grain mills. They used data from the What We Eat in America study to estimate consumption rates of water and rice across the population. Based on their results, average inorganic arsenic exposure from water and rice were 4.2 mcg/day and 1.4 mcg/day, respectively.

The average exposure from rice was two times as high for Tribal (ie, Native Americans and Native Alaskans), Asian, and Pacific Islander populations compared with the overall US population, indicating that while most Americans don’t consume concerning levels of inorganic arsenic, these populations are more at risk than others. Whether the higher consumption of inorganic arsenic from rice is harmful depends on what other sources of inorganic arsenic exist in the diet and drinking water. If frequent consumption of rice contributes to consuming more than the EPA’s RfD after considering other dietary sources, it may be a concern.

Infants and young children are another population that may consume more arsenic than others. Jara and Winter found that inorganic arsenic exposures for 2-year-old children were 3.3 to 4.8 times higher than the amount exposed to the rest of the US population, albeit still lower than the EPA’s RfD. Higher intakes of inorganic arsenic in young children may be a result of less variety in their diets compared with older populations and more reliance on grain and rice products. The authors concluded that the inorganic arsenic exposures they estimated in 2-year-olds weren’t concerning because they were below the EPA’s RfD.

Possible Health Effects of Arsenic

While the literature on the health effects of arsenic exposure is fairly robust, there are limitations. There are several epidemiologic studies on the relationship between arsenic exposure and cancer, but other health conditions aren’t as well researched. In addition, existing studies largely have focused on inorganic arsenic from drinking water instead of food. More extensive research is needed to fully understand the effects of arsenic in the food and water supply on human health.

Acute arsenic toxicity can lead to vomiting, diarrhea, stomach pain, organ failures, and ultimately death. Although rare, it can occur from accidental ingestion, inhalation, or absorption of high amounts of arsenic that may occur when working in industries such as wood treatment or metal extraction, also known as smelting.

Chronic arsenic toxicity occurs after prolonged exposure to arsenic, leading to its accumulation in the liver, kidneys, muscles, nervous system, hair, and nails. Over time, it can lead to cancers of the skin, liver, lung, kidneys, bladder, and prostate. In fact, inorganic arsenic has been identified as a known human carcinogen. Other arsenic-related diseases include hypertension, skin lesions, diabetes, and atherosclerosis. Cases of chronic arsenic poisoning have occurred in India, Bangladesh, Taiwan, and other countries or areas with extremely contaminated groundwater supplies.

However, the dose-response relationship between arsenic and disease isn’t fully understood. For example, the effects of chronic low-level arsenic exposure aren’t always clear. The EPA’s current RfD of 0.3 mcg of inorganic arsenic per kilogram of body weight per day is “an estimate of a daily exposure to the human population that’s likely to be without appreciable risk of deleterious noncancer effects during a lifetime.” The following sections review the current research on arsenic and disease, including possible mechanisms of action.

Cancer

The metabolism of inorganic arsenic in the body involves methylation that yields toxic arsenic metabolites, including reactive oxygen species, that interfere with gene expression, inhibit enzymatic reactions, and lead to cellular oxidative damage. These carcinogenic effects exhibited by arsenic may play a large role in the development of cancers, especially of the skin, lung, and bladder.

The previously noted associations between cancer and high arsenic exposures are based on research from areas with highly contaminated water sources. Studies that have focused on the United States, where arsenic exposures generally are low, suggest that lower arsenic exposures may not be linked to increased cancer risk, but the results are conflicting.34,35

In an analysis of inorganic arsenic in drinking water and lung cancer over 30 years in the United States, Ferdosi and colleagues found no association between an increased risk of lung cancer and inorganic arsenic exposure in the range of 3 to 59 mcg/L of water.34 This research supports similar findings suggesting cancer risk doesn’t increase with arsenic exposures below 100 to 150 mcg/L.

On the other hand, a systematic review of studies that analyzed relationships between bladder and kidney cancer and arsenic in water found that lower exposures to arsenic may be a significant issue. The results suggested that 10 mcg/L of arsenic in drinking water, the current EPA MCL, can increase the risk of bladder cancer by 40% to 100%. The study also found that those exposed to water with arsenic concentrations greater than 150 mcg/L had a 30% higher risk of dying from bladder or kidney cancer compared with those exposed to water with 10 mcg/L. Finally, some research suggests there are correlations between incidence of skin cancer and arsenic concentrations less than 10 mcg/L.

Heart Disease and Hypertension

While the mechanism of action isn’t fully understood concerning the effect of arsenic on the cardiovascular system, arsenic may increase blood pressure by promoting oxidative stress, inhibiting vasorelaxation, and possibly preventing the creation of nitric oxide. Arsenic may contribute to atherosclerosis by increasing blood levels of proinflammatory cytokines and decreasing cholesterol efflux, or the ability of HDL to remove cholesterol from plaques.

Research suggests that high arsenic exposure levels are associated with increased odds of developing hypertension but that the low to moderate exposure levels typical in the United States are not. One study including more than 4,000 US adults found no associations between different measures of urinary arsenic and the prevalence of hypertension. On the other hand, a study that analyzed urine arsenic levels in pregnant women who lived in areas of New Hampshire with water arsenic levels above the 10 ppb EPA MCL found that an increase of 5 mcg/L of urinary arsenic was associated with a significant increase in systolic blood pressure per month throughout pregnancy. The conflicting results of existing research on arsenic and hypertension further illuminate that the effects of arsenic seem to largely depend on the level of exposure.

Type 2 Diabetes

Some research suggests that arsenic may prevent both the uptake of glucose from the bloodstream and the release of insulin from the pancreas.

Consumption of drinking water with levels of inorganic arsenic over 500 mcg/L has been linked to type 2 diabetes, but it’s unclear whether water with levels below 100 mcg/L, which many studies use as a measure of “low” exposure, presents a risk.

A case-cohort study that included participants from the San Luis Valley of Colorado found that even low-level inorganic arsenic exposure from drinking water is significantly associated with risk of diabetes over time. The results showed a hazard ratio of 1.59, or a 59% higher risk of developing diabetes, per every 15 mcg/L of inorganic arsenic. While these results provide valuable insight, more research is needed to help clarify the relationship between arsenic and diabetes.

Neurodevelopment and Mental Health

Exposure to arsenic during critical times of neurodevelopment, including pregnancy and childhood, can have damaging effects. Arsenic can cross the placenta and therefore disrupt the development of the central nervous system, potentially leading to cognitive impairments and disabilities. If children continue to be exposed to arsenic in early life, the damaging effects will continue. In particular, arsenic can stimulate the production of free radicals that contribute to neuron death, decrease levels of neurotransmitters, and impair the formation of the myelin sheath.

Most of the research linking neurodevelopment issues and arsenic exposure has focused on areas with high levels of inorganic arsenic contamination in the drinking water or soil, such as parts of South Asia or rural areas of the United States. Researchers who assessed 524 children aged 2 to 3 in Bangladesh found that increased levels of arsenic in the family’s drinking water throughout the first 20 to 40 months of life were significantly associated with decreased cognitive scores. The median water arsenic concentration in the Pabna District of Bangladesh analyzed in the study was 25.7 mcg/L.

A cohort study with close to 4,000 mothers and children who lived in South Carolina during their early life found that the odds of intellectual disability were 13% higher for each unit of arsenic (mg/kg) found in the soil of the area. However, the study also examined other heavy metals, making it difficult to assess the effects of arsenic in isolation.

Adults exposed to high levels of arsenic also may experience issues related to neurodevelopment, including mental health disorders. One study conducted in India with 1,477 adults who suffered chronic arsenic poisoning from contaminated well water found that close to 19% of the participants had depression, anxiety, or other psychiatric problems. This was much higher than the 7% prevalence of mental health disorders in the rest of the country.

While there are several studies on the association between arsenic and neurotoxicity, the exact dose-response relationship is unclear. The level of inorganic arsenic exposure that significantly increases the risk of cognitive and mental health issues continues to be explored.

Special Populations to Consider

Inorganic arsenic exposure at any stage of the lifecycle is concerning, but there are some populations at greater risk of exposure.

Young children may be especially susceptible to the negative effects of arsenic, particularly in regard to neurodevelopment. This population has limited variety in their diets and may consume large amounts of rice cereal and rice products. Since children weigh less than adults, the EPA’s RfD of 0.3 mcg of arsenic per kilogram of body weight per day translates to a smaller allowable maximum of arsenic from food and water.

Pregnant women also are a vulnerable population, especially because arsenic can pass through the placenta to developing embryos. Research suggests arsenic also can pass through breastmilk, but fortunately in low concentrations. Breast-feeding is likely still safe, even in areas with high arsenic contamination.

Cultures that eat large amounts of rice may consume more arsenic than do other populations. This includes individuals of all ages, but especially young children, in Asian, Pacific Islander, and Native American populations.

Finally, residents of “hot spot” communities with drinking water containing levels of inorganic arsenic that greatly exceeds the EPA standard of 10 ppb may be especially susceptible to associated negative health outcomes. Susceptibility increases when any of the above populations overlap with a geographical area that has high-level arsenic concentrations in the water and soil.

Source: Today’s Dietitian

Study Uncovers New Link Between Long-term Arsenic Exposure and Type 2 Diabetes

A University of Arizona Health Sciences study has identified the biological mechanism linking long-term arsenic exposure to diseases such as cancer and Type 2 diabetes. The findings could result in potential new targets for drug development.

More than 34 million Americans have diabetes, according to the Centers for Disease Control and Prevention, and approximately 90-95% of them have Type 2 diabetes. One of the main risk factors is environmental toxicant exposure, particularly chronic exposure to arsenic, which has been shown to affect insulin production and sensitivity, blood sugar levels, and lipid profiles, all common features of diabetes onset and progression.

Because arsenic is a natural metalloid found in soil, it can be one of the most significant contaminants in drinking water globally, especially when ingested at unsafe levels. Arsenic is present in almost all groundwater sources in Arizona, particularly in rural areas. Combined with occupational exposures, such as mining, more than 160 million people worldwide are exposed to arsenic.

New research led by Donna D. Zhang, PhD, the Musil Family Endowed Chair in Drug Discovery at the UArizona College of Pharmacy and a member of the BIO5 Institute, uncovered a biological mechanism by which chronic arsenic exposure led to insulin resistance and glucose intolerance, two key features of diabetes progression.

The study examined the effect of arsenic exposure on nuclear factor-erythroid 2 related factor 2 (NRF2) activation. NRF2 is a protein that plays an important role in maintaining cellular homeostatis, especially during times of oxidative stress when there is an imbalance of free oxygen radicals and antioxidants in the body.

Long-term oxidative stress, such as that caused by cigarette smoke, radiation, diets high in sugar, fat and alcohol, or environmental toxins, contributes to the development of a range of chronic conditions including cancer, diabetes and neurodegenerative disease.

NRF2 is the body’s governing regulator against oxidative stress. When the body enters an oxidative stress state, NRF2 is activated and the process of cellular protection begins. When cellular homeostatis is restored, NRF2 levels return to normal.

Dr. Zhang and the research team found that arsenic exposure results in the prolonged and uncontrolled activation of NRF2, which previously was determined to be a driver of cancer progression and resistance to anti-cancer therapy. In this study, they found that arsenic exposure resulted in glucose intolerance and decreased insulin sensitivity. In particular, prolonged NRF2 activation by chronic arsenic exposure caused shifts in pathways that control amino acid, fatty acid, carbohydrate, lipid and drug metabolism.

The findings demonstrated that prolonged NRF2 activation in response to arsenic increased glucose production in the liver and the release of that glucose to the bloodstream, which could represent a key driver of changes in systemic blood glucose.

“Hopefully this study will serve as a foundation for future toxicant-driven diabetes research here at the University of Arizona Health Sciences and elsewhere,” said Dr. Zhang, who also is an associate director of the UArizona Superfund Research Center. “Our eventual goal is to generate effective preventive or interventive strategies to treat exposed populations.”

This study was published in Molecular Metabolism.

Source: The University of Arizona

Coconut Ice Cream with Mango Sauce

Ingredients

4 egg yolks
1/2 cup cater sugar
1 tbsp cornstarch
1 tsp almond essence
2-1/2 cups milk
1-1/2 cups freshly grated coconut, or grated creamed coconut
1-1/4 cups whipping cream

Mango Sauce

1 large ripe mango
2 tbsp caster sugar
1 tbsp lemon juice
4 tbsp fresh orange juice

Method

  1. Beat the egg yolks, sugar, cornstarch, almond essence and a little of the milk until combined.
  2. If using freshly grated coconut, tip it into a food processor and process with 1-1/4 cups of the remaining milk until fairly smooth.
  3. Pour the fresh coconut milk into a heavy-based saucepan and stir in the rest of the milk. If using creamed coconut, simply heat it with the milk, stirring frequently. Bring the milk almost to the boil.
  4. Gradually pour the milk over the egg yolks whisking constantly. Return the mixture to the pan and cook very gently, stirring until thickened.
  5. Pour the custard into a bowl, cover it with a circle of greaseproof paper and leave to cool.
  6. Pour the cream into the ice cream maker and churn until it holds its shape. Spoon into a freezer container and freeze for several hours or overnight.
  7. Make the sauce. Slice the mango flesh off the stone and put it into a food processor. Add the sugar, lemon juice and orange juice and process until smooth. Pour into a small jug and chill.
  8. To serve, scoop the prepared ice cream into the halved coconut shells, or into tall serving glasses. Add the mango sauce and serve immediately.

Makes 6 servings.

Source: ICe Cream and Iced Desserts


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